- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01605396
A Phase II Trial of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in Participants With Breast Cancer (MK-8669-064)
A Phase II Randomized Trial of the Combination of Ridaforolimus and Exemestane, Compared to Ridaforolimus, Dalotuzumab and Exemestane in High Proliferation, Estrogen Receptor Positive Breast Cancer Patients
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Females with a histologically confirmed diagnosis of breast cancer that is metastatic or locally advanced (locally advanced tumors must not be amenable to
surgery or radiation therapy with curative intent) with the following pathological characteristics determined locally: estrogen receptor positive and Human Epidermal Growth Factor Receptor 2 (HER-2) negative, and Ki67 (a tumor marker) ≥ 15% determined by the central study laboratory
- Post-menopausal
- With advanced breast cancer whose disease was refractory to previous letrozole or anastrozole
- Has at least one confirmed measurable metastatic lesion
- Has a performance status ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Has a life expectancy of at least 3 months
- Adequate organ function
Exclusion Criteria:
- Is receiving any other concurrent systemic tumor therapy, including
hormonal agents and HER-2 inhibitors
- Previously received rapamycin or rapamycin analogs, including
ridaforolimus, temsirolimus, or everolimus
- Received prior treatment with Insulin-like Growth Factor 1 Receptor (IGF-1R) inhibitors, Phosphatidylinositol 3-Kinase (PI3K) inhibitors, or
other experimental agents that target PI3K, Protein Kinase B (AKT), or Mammalian Target of Rapamycin (mTOR) pathway
- Is receiving chronic corticosteroids administered at doses greater than
those used for normal replacement therapy
- Has active brain metastasis or leptomeningeal carcinomatosis; patients
with adequately treated brain metastases are eligible if they meet certain criteria
- Known allergy to macrolide antibiotics
- Has an active infection requiring antibiotics
- Significant or uncontrolled cardiovascular disease
- Poorly controlled Type 1 or 2 diabetes
- Is known to be Human Immunodeficiency Virus (HIV) positive
- Has a known history of active hepatitis B or C. Healthy carriers of hepatitis B are not allowed on this study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ridaforolimus + Dalotuzumab + Exemestane
Participants receive ridaforolimus 10 mg orally (PO) every 5 days (QD x 5) plus dalotuzumab 10 mg/kg intravenously (IV) every week (QW) plus exemestane 25 mg PO every day (QD) in 28-day cycles until documented disease progression or unacceptable toxicity.
|
Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, & 22-26 of 28-day cycle.
Other Names:
Dalotuzumab administered 10 mg/kg IV weekly on Days 1, 8, 15, and 22 of 28-day cycle.
Other Names:
Exemestane 25 mg tablet administered PO QD.
Other Names:
|
Active Comparator: Ridaforolimus + Exemestane
Participants receive ridaforolimus 30 mg PO QD x 5 plus exemestane 25 mg PO QD treatment in 28-day cycles until documented disease progression or unacceptable toxicity.
|
Ridaforolimus 10 mg tablet, administered PO at a dose of 10 mg (triplet) or 30 mg (doublet) depending upon randomization, on Days 1-5, 8-12, 15-19, & 22-26 of 28-day cycle.
Other Names:
Exemestane 25 mg tablet administered PO QD.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
1. Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)
Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
|
PFS was defined as the time from randomization to progressive disease, or death, whichever occurs first.
Response was assessed according to RECIST 1.1 by BICR.
According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of >5 mm in the SOD, or the appearance of new lesions.
PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval [CI]) in weeks was reported for each treatment arm.
Per protocol, participants remained on assigned treatment until disease progression.
Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression.
All participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
|
From Day 1 through last post-study efficacy follow-up (up to ~19 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in Sum of Target Lesion Diameters at Week 16
Time Frame: Baseline, Week 16
|
The percent change from baseline to Week 16 in the sum of target lesion diameters as determined by anatomic imaging was defined as the line length (i.e., diameter) for each target lesion identified at baseline summed across all lesions at baseline, and separately at each post-baseline time point.
The primary analysis was conducted using a constrained longitudinal data analysis (cLDA) method and target lesion measurements according to the BICR.
Percent change from baseline in sum of target lesion diameters at Week 16 was reported for each treatment arm.
|
Baseline, Week 16
|
3. Percentage of Participants With Objective Response (Objective Response Rate [ORR]) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR).
Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
|
ORR was defined as the percentage of participants whose best response was complete response (CR; disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal) or partial response (PR; at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 and based on BICR.
ORR was reported for each treatment arm.
Per protocol, participants remained on assigned treatment until disease progression.
Participants who discontinued study treatment for reasons other than disease progression continued to be assessed by imaging until objective documentation of progression.
|
From Day 1 through last post-study efficacy follow-up (up to ~19 months)
|
Overall Survival (OS)
Time Frame: From Day 1 through last post-study efficacy follow-up (up to ~19 months)
|
OS was defined as the time from randomization to death due to any cause.
Participants without documented death at the time of analysis were censored at the date last known to be alive.
OS was analyzed using the Kaplan-Meier method and median OS (95% confidence interval [CI]) in weeks was reported for each treatment arm.
Per protocol, all participants (including participants who discontinued study treatment) were followed for survival until investigator notification to discontinue.
|
From Day 1 through last post-study efficacy follow-up (up to ~19 months)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Exemestane
Other Study ID Numbers
- 8669-064
- 2012-000335-11 (EudraCT Number)
- MK-8669-064 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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